Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions
Lemire, J.M.; Archer, D.C.; Beck, L.; Spiegelberg, H.L.
Journal of Nutrition 125(6 Suppl): 1704s-1708s
1995
ISSN/ISBN: 0022-3166 PMID: 7782931 Document Number: 441413
1,25-Dihydroxyvitamin D-3 (1,25-(OH)-2D-3) is known to be an immunosuppressive hormone. This review primarily deals with in vitro and in vivo effects of 1,25-(OH)-2-D-3 and analogue, 1,25-dihydroxy-16ene-vitamin D-3 (1,25-(OH)2-16ene-D-3), on T helper subsets type 1 (Th-1) or type 2 (Th-2) that have distinctive functional characteristics in humans. Th-1 secrete interferon (IFN-gamma), interleukin (IL-2) and induce B cells to produce immunoglobulin IgG-2a while Th-2 secrete IL-4, IL-10 and induce the production of IgG-1 and IgE by B cells. The sterol inhibits the secretion of IL-12, a cytokine produced by monocytes and B cells, which leads to the activation and differentiation of Th-1. In addition, 1,25-(OH)-2-D-3 directly inhibits IFN-gamma secretion by Th-1 clones while it has little effect on IL-4 secretion by Th-2 clones. The analogue, 1,25-(OH)-2-16ene-D-3, is 100-fold more potent than 1,25-(OH)2-D-3 in inhibiting IFN-gamma secretion but also has little effect on IL-4 secretion. In mice, when given in vivo, the sterol prevents the induction of spontaneous and induced autoimmune diseases and inhibits Th, induce IgG-2a. responses. These actions of the vitamin D-3 compounds suggest that it may have potential therapeutic applications in Th-1-mediated clinical situations such as autoimmunity and transplantation.